chr1-196944067-C-G

Variant names:

• chr1-196944067-C-G
• rs140103005
• NM_005666.4:c.58+129C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005666.4(CFHR2):​c.58+129C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (9176 hom., cov: 15)
  • Exomes 𝑓: 0.41 (27019 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFHR2 NM_005666.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.258
• Publications: 2 publications found

Genes affected

CFHR2 (HGNC:4890): (complement factor H related 2) This gene belongs to a family of complement factor H-related genes (CFHR), which are clustered together with complement factor H gene on chromosome 1, and are involved in regulation of complement. Mutations in CFHR genes have been associated with dense deposit disease and atypical haemolytic-uraemic syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-196944067-C-G is Benign according to our data. Variant chr1-196944067-C-G is described in ClinVar as Benign. ClinVar VariationId is 1271113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005666.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR2	NM_005666.4	MANE Select	c.58+129C>G		intron	N/A	NP_005657.1	P36980-1
	CFHR2	NM_001410924.1		c.58+129C>G		intron	N/A	NP_001397853.1	A0A3B3IRW0
	CFHR2	NM_001312672.1		c.58+129C>G		intron	N/A	NP_001299601.1	A0A3B3IS28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR2	ENST00000367415.8	TSL:1 MANE Select	c.58+129C>G		intron	N/A	ENSP00000356385.4	P36980-1
	CFHR2	ENST00000367421.5	TSL:1	c.58+129C>G		intron	N/A	ENSP00000356391.4	A0A3B3IQ51
	CFHR2	ENST00000473386.1	TSL:1	c.58+129C>G		intron	N/A	ENSP00000497089.1	A0A3B3IS28

Frequencies

GnomAD3 genomes AF: 0.368 AC: 35058 AN: 95394 Hom.: 9169 Cov.: 15

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.394

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.413 AC: 90825 AN: 219686 Hom.: 27019 AF XY: 0.415 AC XY: 48494 AN XY: 116774

African (AFR) AF: 0.526 AC: 1616 AN: 3072

American (AMR) AF: 0.600 AC: 6613 AN: 11024

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 2465 AN: 5312

East Asian (EAS) AF: 0.827 AC: 15177 AN: 18352

South Asian (SAS) AF: 0.462 AC: 11349 AN: 24558

European-Finnish (FIN) AF: 0.370 AC: 7450 AN: 20154

Middle Eastern (MID) AF: 0.323 AC: 209 AN: 648

European-Non Finnish (NFE) AF: 0.329 AC: 41188 AN: 125136

Other (OTH) AF: 0.416 AC: 4758 AN: 11430

GnomAD4 genome AF: 0.368 AC: 35076 AN: 95428 Hom.: 9176 Cov.: 15 AF XY: 0.381 AC XY: 17605 AN XY: 46244

African (AFR) AF: 0.439 AC: 7134 AN: 16264

American (AMR) AF: 0.490 AC: 4818 AN: 9824

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 965 AN: 2390

East Asian (EAS) AF: 0.730 AC: 2943 AN: 4032

South Asian (SAS) AF: 0.414 AC: 1194 AN: 2886

European-Finnish (FIN) AF: 0.348 AC: 2660 AN: 7650

Middle Eastern (MID) AF: 0.273 AC: 48 AN: 176

European-Non Finnish (NFE) AF: 0.293 AC: 14710 AN: 50174

Other (OTH) AF: 0.390 AC: 488 AN: 1252

Alfa AF: 0.325 Hom.: 1233

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.80
PhyloP100		-0.26
PromoterAI		0.0011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs140103005; hg19: chr1-196913197; COSMIC: COSV66380837;